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The relationship between transcription and eccentricity in human V1

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Abstract

Gene expression gradients radiating from regions of primary sensory cortices have recently been described and are thought to underlie the large-scale organization of the human cerebral cortex. However, the role of transcription in the functional layout of a single region within the adult brain has yet to be clarified, likely owing to the difficulty of identifying a brain region anatomically consistent enough across individuals with dense enough tissue sampling. Overcoming these hurdles in human primary visual cortex (V1), we show a relationship between differential gene expression and the cortical layout of eccentricity in human V1. Interestingly, these genes are unique from those previously identified that contribute to the positioning of cortical areas in the visual processing hierarchy. Enrichment analyses show that a subset of the identified genes encode for structures related to inhibitory interneurons, ion channels, as well as cellular projections, and are expressed more in foveal compared to peripheral portions of human V1. These findings predict that tissue density should be higher in foveal compared to peripheral V1. Using a histological pipeline, we validate this prediction using Nissl-stained sections of postmortem occipital cortex. We discuss these findings relative to previous studies in non-human primates, as well as in the context of an organizational pattern in which the adult human brain employs transcription gradients at multiple spatial scales: across the cerebral cortex, across areas within processing hierarchies, and within single cortical areas.

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Data availability

All analyzed data were curated from the following open datasets. Allen Human Brain Atlas (AHBA) Microarray Data: http://human.brain-map.org. Neuropythy atlas of human visual cortex: https://github.com/noahbenson/neuropythy. BrainSpan histological stains: http://www.brainspan.org/static/atlas.

Code availability

Code related to processing of AHBA transcription data can be found on author ZZ’s GitHub at: https://github.com/zhenzonglei/matni, and code for the beta version of BrainWalker can be found at: https://github.com/gomezj/geneccentricity.

References

  • Alvarez I, Finlayson NJ, Ei S, de Haas B, Greenwood JA, Schwarzkopf DS (2021) Heritable functional architecture in human visual cortex. NeuroImage 239:118286.

    Article  PubMed  Google Scholar 

  • Amunts K, Zilles K (2015) Architectonic mapping of the human brain beyond brodmann. Neuron 88:1086–1107

    Article  CAS  PubMed  Google Scholar 

  • Arcaro MJ, Kastner S (2015) Topographic organization of areas V3 and V4 and its relation to supra-areal organization of the primate visual system. Vis Neurosci 32:E014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Arnatkeviciute A, Fulcher BD, Fornito A (2019) A practical guide to linking brain-wide gene expression and neuroimaging data. Neuroimage 189:353–367

    Article  PubMed  Google Scholar 

  • Azzopardi P, Jones KE, Cowey A (1999) Uneven mapping of magnocellular and parvocellular projections from the lateral geniculate nucleus to the striate cortex in the macaque monkey. Vision Res 39:2179–2189

    Article  CAS  PubMed  Google Scholar 

  • Balaram P, Kaas JH (2014) Towards a unified scheme of cortical lamination for primary visual cortex across primates: insights from NeuN and VGLUT2 immunoreactivity. Front Neuroanat 8:81

    Article  PubMed  PubMed Central  Google Scholar 

  • Barone P, Debay C, Berland M, Kennedy H (1996) Role of directed growth and target selection in the formation of cortical pathways: prenatal development of the projection of area V2 to area V4 in the monkey. J Comp Neurol 374:1–20

    Article  CAS  PubMed  Google Scholar 

  • Batardiere A, Barone P, Dehay C, Kennedy H (1998) Area-specific laminar distribution of cortical feedback neurons projecting to cat area 17: quantitative analysis in the adult and during ontogeny. J Comp Neurol 396:493–510

    Article  CAS  PubMed  Google Scholar 

  • Benson NC, Winawer J (2018) Bayesian analysis of retinotopic maps. Elife 7:e40224

    Article  PubMed  PubMed Central  Google Scholar 

  • Benson NC et al (2021) Variability of the surface area of the V1, V2, and V3 maps in a large sample of human observers. bioRxiv 109:816

    Google Scholar 

  • Burt JB et al (2018) Hierarchy of transcriptomic specialization across human cortex captured by structural neuroimaging topography. Nat Neurosci 93:165

    Google Scholar 

  • Chen J, Bardes EE, Aronow BJ, Jegga AG (2009) ToppGene Suite for gene list enrichment analysis and candidate gene prioritization. Nucleic Acids Res 37:W305-311

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Collins CE, Airey DC, Young NA, Leitch DB, Kaas JH (2010) Neuron densities vary across and within cortical areas in primates. Proc Natl Acad Sci U S A 107:15927–15932

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Collins CE, Turner EC, Sawyer EK, Reed JL, Young NA, Flaherty DK, Kaas JH (2016) Cortical cell and neuron density estimates in one chimpanzee hemisphere. Proc Nat Acad Sci 113(3):740–745

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dale AM, Fischl B, Sereno MI (1999) Cortical surface-based analysis I. Segmentation and surface reconstruction. Neuroimage 9:179–194

    Article  CAS  PubMed  Google Scholar 

  • Eickhoff SB, Rottschy C, Zilles K (2007) Laminar distribution and co-distribution of neurotransmitter receptors in early human visual cortex. Brain Struct Funct 212:255–267

    Article  CAS  PubMed  Google Scholar 

  • Eickhoff SB, Yeo BTT, Genon S (2018) Imaging-based parcellations of the human brain. Nat Rev Neurosci 19:672–686

    Article  CAS  PubMed  Google Scholar 

  • Fischl MI, Sereno AM, Dale, (1999) Cortical surface-based analysis. II: inflation, flattening, and a surface-based coordinate system. Neuroimage 9:195–207

    Article  CAS  PubMed  Google Scholar 

  • Fornito A, Arnatkeviciute A, Fulcher BD (2019) Bridging the gap between connectome and transcriptome. Trends Cogn Sci 23:34–50

    Article  PubMed  Google Scholar 

  • Fulcher BD (2019) Discovering conserved properties of brain organization through multimodal integration and interspecies comparison. J Exp Neurosci 13:1179069519862047

    Article  PubMed  PubMed Central  Google Scholar 

  • Gomez J, Natu V, Jeska B, Barnett M, Grill-Spector K (2018) Development differentially sculpts receptive fields across early and high-level human visual cortex. Nat Commun 9:788

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Gomez J et al (2019) Development of population receptive fields in the lateral visual stream improves spatial coding amid stable structural-functional coupling. Neuroimage 188:59–69

    Article  PubMed  Google Scholar 

  • Gomez J, Zhen Z, Weiner KS (2019) Human visual cortex is organized along two genetically opposed hierarchical gradients with unique developmental and evolutionary origins. PLoS Biol. 17:e3000362

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hawrylycz MJ et al (2012) An anatomically comprehensive atlas of the adult human brain transcriptome. Natures 489:391–399

    Article  CAS  Google Scholar 

  • Honig LS, Herrmann K, Shatz CJ (1996) Developmental changes revealed by immunohistochemical markers in human cerebral cortex. Cereb Cortex 6:794–806

    Article  CAS  PubMed  Google Scholar 

  • Horiguchi H, Nakadomari S, Misaki M, Wandell BA (2009) Two temporal channels in human V1 identified using fMRI. Neuroimage 47:273–280

    Article  PubMed  Google Scholar 

  • Huntenburg JM, Bazin PL, Margulies DS (2018) Large-scale gradients in human cortical organization. Trends Cogn Sci 22:21–31

    Article  PubMed  Google Scholar 

  • Jones AR, Overly CC, Sunkin SM (2009) The Allen Brain Atlas: 5 years and beyond. Nat Rev Neurosci 10:821–828

    Article  CAS  PubMed  Google Scholar 

  • Kennedy H, Dehay C, Bullier J (1986) Organization of the callosal connections of visual areas V1 and V2 in the macaque monkey. J Comp Neurol 247:398–415

    Article  CAS  PubMed  Google Scholar 

  • Khrameeva E et al (2020) Single-cell-resolution transcriptome map of human, chimpanzee, bonobo, and macaque brains. Genome Res 30:776–789

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kohonen T (1982) Self-organized formation of topologically correct feature maps. Biol Cybern 43:59–69

    Article  Google Scholar 

  • Krienen FM, Yeo BT, Ge T, Buckner RL, Sherwood CC (2016) Transcriptional profiles of supragranular-enriched genes associate with corticocortical network architecture in the human brain. Proc Natl Acad Sci U S A 113:E469-478

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Perkel DJ, Bullier J, Kennedy H (1986) Topography of the afferent connectivity of area 17 in the macaque monkey: a double-labelling study. J Comp Neurol 253:374–402

    Article  CAS  PubMed  Google Scholar 

  • Rakic P, Goldman-Rakic PS, Gallager D (1988) Quantitative autoradiography of major neurotransmitter receptors in the monkey striate and extrastriate cortex. J Neurosci 8:3670–3690

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rosa MG (2002) Visual maps in the adult primate cerebral cortex: some implications for brain development and evolution. Braz J Med Biol Res 35:1485–1498

    Article  CAS  PubMed  Google Scholar 

  • Rosa MG, Tweedale R (2005) Brain maps, great and small: lessons from comparative studies of primate visual cortical organization. Philos Trans R Soc Lond B Biol Sci 360:665–691

    Article  PubMed  PubMed Central  Google Scholar 

  • Schleicher AZ, Zilles K, Wree A (1986) A quantitative approach to cytoarchitectonics: software and hardware aspects of a system for the evaluation and analysis of structural inhomogeneities in nervous tissue. J Neurosci Methods 18:221–235

    Article  CAS  PubMed  Google Scholar 

  • Schwarzkopf DS, Song C, Rees G (2011) The surface area of human V1 predicts the subjective experience of object size. Nat Neurosci 14:28–30

    Article  CAS  PubMed  Google Scholar 

  • Seidlitz J et al (2020) Transcriptomic and cellular decoding of regional brain vulnerability to neurogenetic disorders. Nat Commun 11:3358

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sestan N, Rakic P, Donoghue MJ (2001) Independent parcellation of the embryonic visual cortex and thalamus revealed by combinatorial Eph/ephrin gene expression. Curr Biol 11:39–43

    Article  CAS  PubMed  Google Scholar 

  • Smart IHM, McSherry GM (1986) Gyrus formation in the cerebral cortex of the ferret. Description of the internal histological changes. J Anat 147:27–43

    CAS  PubMed  PubMed Central  Google Scholar 

  • Stigliani A, Jeska B, K, (2017) Grill-spector, encoding model of temporal processing in human visual cortex. Proc Nat Acad Sci 41:788

    Google Scholar 

  • Syken J, Grandpre T, Kanold PO, Shatz CJ (2006) PirB restricts ocular-dominance plasticity in visual cortex. Science 313:1795–1800

    Article  CAS  PubMed  Google Scholar 

  • Takahata T, Shukla R, Yamamori T, Kaas JH (2012) Differential expression patterns of striate cortex-enriched genes among Old World, New World, and prosimian primates. Cereb Cortex 22(10):2313–2321

    Article  PubMed  Google Scholar 

  • Valk SL et al (2020) Shaping brain structure: genetic and phylogenetic axes of macroscale organization of cortical thickness. Sci Adv 6:eabb3417

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wandell BA, Winawer J (2011) Imaging retinotopic maps in the human brain. Vision Res 51:718–737

    Article  PubMed  Google Scholar 

  • Wandell BA, Winawer J (2015) Computational neuroimaging and population receptive fields. Trends Cogn Sci 19:349–357

    Article  PubMed  PubMed Central  Google Scholar 

  • Watakabe A (2009) Comparative molecular neuroanatomy of mammalian neocortex: what can gene expression tell us about areas and layers? Dev Growth Differ 51:343–354

    Article  PubMed  Google Scholar 

  • Watakabe A et al (2007) Comparative analysis of layer-specific genes in Mammalian neocortex. Cereb Cortex 17:1918–1933

    Article  PubMed  Google Scholar 

  • Wei Y et al (2019) Genetic mapping and evolutionary analysis of human-expanded cognitive networks. Nat Commun 10:4839

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Yamamori T, Rockland KS (2006) Neocortical areas, layers, connections, and gene expression. Neurosci Res 55:11–27

    Article  CAS  PubMed  Google Scholar 

  • Zilles K, Palomero-Gallagher N (2017) Multiple transmitter receptors in regions and layers of the human cerebral cortex. Front Neuroanat 11:78

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Funding

This work was supported by (1) start-up funds provided by the University of California, Berkeley and the Helen Wills Neuroscience Institute to KSW; (2) start-up funds provided by Princeton Neuroscience Institute to JG; and (3) The National Natural Science Foundation of China 31771251 awarded to ZZ. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Authors and Affiliations

  1. Princeton Neuroscience Institute, Princeton University, Princeton, NJ, USA

    Jesse Gomez

  2. Psychology Department, Princeton University, Princeton, NJ, USA

    Jesse Gomez

  3. Beijing Key Laboratory of Applied Experimental Psychology, Beijing Normal University, Beijing, China

    Zonglei Zhen

  4. Faculty of Psychology, Beijing Normal University, Beijing, China

    Zonglei Zhen

  5. Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, CA, USA

    Kevin S. Weiner

  6. Psychology Department, University of California Berkeley, Berkeley, CA, USA

    Kevin S. Weiner

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  1. Jesse Gomez
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  2. Zonglei Zhen
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  3. Kevin S. Weiner
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Correspondence to Zonglei Zhen.

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Gomez, J., Zhen, Z. & Weiner, K.S. The relationship between transcription and eccentricity in human V1. Brain Struct Funct 226, 2807–2818 (2021). https://doi.org/10.1007/s00429-021-02387-5

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